13065878 - (D) (P.T.A.B. Mar. 25, 2019)

Ex Parte Gallagher et al

Patent Trials and Appeals BoardMar 25, 2019

13065878 - (D) (P.T.A.B. Mar. 25, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/065,878 03/31/2011 81033 7590 03/27/2019 Medical Diagnostic Laboratories, LLC 2439 Kuser Road Hamilton, NJ 08690 FIRST NAMED INVENTOR Grant Gallagher UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www .uspto.gov ATTORNEY DOCKET NO. CONFIRMATION NO. MDL-00042 3361 EXAMINER JIANG,DONG ART UNIT PAPER NUMBER 1646 NOTIFICATION DATE DELIVERY MODE 03/27/2019 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): jdowning@mdlab.com tbogie@mdlab.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GRANT GALLAGHER, RAYMOND YU, and JONATHAN BRAZAITIS 1 Appeal2018-000349 Application 13/065,878 Technology Center 1600 Before ERIC B. GRIMES, TA WEN CHANG, and RYAN H. FLAX, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. Â§ 134 involving claims to a pharmaceutical composition and a method of making it, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. Â§ 6(b ). We reverse. STATEMENT OF THE CASE "IL-23 is speculated to play an essential role in chronic inflammation and autoimmune diseases in humans." Spec. ,r 6. "IL-23 exerts its biological activities by binding to IL-23 receptor (IL-23R). IL-23R comprises an 1 Appellants identify the Real Party in Interest as Medical Diagnostic Laboratories LLC. Br. 4. Appeal2018-000349 Application 13/065,878 IL-23Ra subunit and an IL-I2RBI subunit." Id. ,r 7. "Human IL-23Ra mRNA is 2.8kb long and contains 11 exons (NM_I44701). The translated full-length IL-23Ra protein is a type-I transmembrane protein (629 amino acids)." Id. ,r 8. The invention "relates to ... a soluble translated form (e.g., L'i9 or L'i8,9) [that exists] as a result of the alternative splicing of the IL-23Ra gene. It exists as a naturally-occurring soluble truncated form of IL-23Ra ... [and] is useful as a therapeutic agent ... in immunological diseases." Id. ,r 4. Claims 24--28 and 34--42 are on appeal. Claim 24 is illustrative and reads as follows ( emphasis added): 24. A pharmaceutical composition useful in inhibiting IL-23R mediated cell signaling, comprising a recombinant IL-23Ra protein, said recombinant IL-23Ra protein consists of the amino acid sequence of SEQ ID NO: 4, and a pharmaceutical acceptable excipient. Claim 42, the only other independent claim, is directed to a method of making a pharmaceutical composition comprising the same IL-23Ra protein as recited in claim 24 by recombinantly expressing the protein, isolating it, and combining it with a pharmaceutically acceptable excipient. DISCUSSION The Examiner has rejected all of the claims on appeal under 35 U.S.C. Â§ I03(a) as obvious based on Kan2 and Cosman. 3 Ans. 2. The Examiner finds that "Kan discloses that the signalling of IL-23 and its receptor (IL- 23R) ... plays a pivotal role in human inflammatory and autoimmune 2 S-h Kan et al., Identification and characterization of multiple splice forms of the human interleukin-23 receptor a chain in mitogen-activated leukocytes, 9 GENES AND IMMUNITY, 631-39 (2008). 3 Cosman et al., US 2003/0059871 Al, publ. Mar. 27, 2003. 2 Appeal2018-000349 Application 13/065,878 responses." Ans. 2. "Kan identifies the human IL-23Ra (wild-type) and multiple splice forms/variants thereof." Id. The Examiner finds that "Kan teaches that five splice variants are of interest because of their yielding potentially functional transcripts: 1'17; 1'19; 1'18,9; ... , which are potentially able to encode soluble forms of IL-23Ra; the first three transcripts are very likely to be translated to various IL-23Ra protein 'early termination' variants." Id. at 2-3. "[T]hese potential soluble receptors generated by exon variants therefore may block IL-23/IL-23R signalling activity by acting as a 'decoy receptor."' Id. at 3. The Examiner finds that the "variant 1'18,9 lacks two consecutive exons 8 and 9, and its amino acid sequence consists of 326 residues, which is a soluble form of the receptor, and has a Genbank Entry Number AM990321," and comparison of that sequence to SEQ ID NO: 4 "reveals that the only difference is at the residue 310: wherein the present SEQ ID N0:4 has Leu at position 310 (representing the wild type of IL-23R), whereas Kan's 1'18,9 encoded by AM990321 has Pro at position 310." Id. The Examiner finds that "Cosman discloses the polypeptides of hematopoietin receptor ( cytokine receptor) family (HPRl and HPR2), wherein the HPR2 polypeptide of SEQ ID N0:21 ... is 100% identical to Kan's human IL-23Ra (wild-type)." Id. at 4. The Examiner also finds that "Cosman teaches naturally occurring genomic variants of the HPR2 sequences, as one example, a change from the Leu residue position 310 of SEQ ID N0:21 to a Pro residue." Id. "In summary, Kan teaches an IL-23Ra 1'18,9 splice variant, which amino acid sequence comprises the same amino acids as that of the present SEQ ID N0:4 with one exception at position 310 (Leu (L)----+ Pro (P)); and 3 Appeal2018-000349 Application 13/065,878 Cosman teaches that this amino acid substitution represents a naturally occurring variant of IL-23Ra." Id. at 5. The Examiner concludes that it would have been obvious "to recombinantly make the soluble IL-23Ra L'i8,9 encoded by Kan's AM990321 (P310), or a soluble IL-23R[a] L'i8,9 comprising L310 (the present SEQ ID N0:4) ... and to make a pharmaceutical composition thereof following the teachings of Kan and Cosman." Id. at 6. The Examiner reasons that a skilled artisan "would have been motivated to do so for the potential therapeutic applications of the soluble receptor as IL-23R mediated signaling is involved in the development of autoimmune diseases, and the L'i8,9 polypeptide is a soluble IL-23Ra and may serve as a decoy receptor for disease treatment (by Kan)." Id. Appellants argue, among other things, that "[t]here is no suggestion, motivation or incentive to combine the cited prior art references to arrive at the recombinant truncated protein IL-23Ra L'i8,9 required in Appellants' claims, i.e., SEQ.ID.N0.:4, for preparing a pharmaceutical composition." Br. 18. Appellants argue that the L'i8,9 isoform taught by Kan (isoform _ v9, with the sequence shown in AM990321 ), "if translated, would encode amino acids 147-326 ... of the present SEQ.ID.N0.:4 with 99.4% identity. The difference in the corresponding amino acid sequences is a change of pro line to leucine at position 310." Br. 21-22. Appellants argue that "[a]bsent Appellants['] disclosure, there is nothing to point one skilled in the art to SEQ ID N0:4." Br. 23. We agree with Appellants that the Examiner has not persuasively shown that the cited references support a prima facie case of obviousness. "During prosecution ... , the PTO gives claims their broadest reasonable 4 Appeal2018-000349 Application 13/065,878 meaning in light of the specification." In re Crish, 393 F.3d 1253, 1257 (Fed. Cir. 2004). In Crish, in a claim reciting "a portion of the nucleotide sequence of SEQ ID NO: 1, wherein said portion consists of the nucleotide sequence from 521 to 2473 of SEQ ID N0:1," id. at 1254, "[t]he reasonable interpretation ... is that the term 'consists' limits the 'said portion' language to the subsequently recited numbered nucleotides." Id. at 1257. The claims at issue here are similar to those of Crish. Thus, in Appellants' claim 24, the recitation of the "recombinant IL-23Ra protein [that] consists of the amino acid sequence of SEQ ID NO: 4" limits the protein in the claimed composition to one that has the single, specific sequence of amino acids recited in SEQ ID NO: 4, without any additions, deletions, or substitutions. As relevant to the rejection on appeal, claim 24 requires a variant of Kan's L'i8,9 isoform in which the pro line at position 310 is replaced with leucine. Kan discloses "human IL23R splice variants resulting from alternative splicing of the IL23R mRNA." Kan 631, abstract. Kan discloses that the L'i8,9 variant is among those that "are potentially able to encode soluble forms of IL-23Ra without the transmembrane and intracellular domains." Id. at 635, left col. Kan states that "[t]hese potential soluble receptors generated by exon variants therefore may block IL-23/IL-23R signalling activity by acting as a 'decoy receptor."' Id. at 636, right col. The Examiner concedes, however, that "the present SEQ ID N0:4 has Leu at position 310 (representing the wild type of IL-23R), whereas Kan's L'i8,9 encoded by AM990321 has Pro at position 310." Ans. 3. The Examiner finds that "Cosman discloses the polypeptides of hematopoietin receptor (cytokine receptor) family (HPRl and HPR2), wherein the HPR2 5 Appeal2018-000349 Application 13/065,878 polypeptide ... is 100% identical to Kan's human IL-23Ra (wild-type)." Ans. 4. The Examiner also finds that "Cosman teaches naturally occurring genomic variants of the HPR2 sequences, as one example, a change from the Leu residue position 310 of SEQ ID N0:21 to a Pro residue." Id. at 4. Based on this teaching, the Examiner concludes that it would have been obvious to make a L'i8,9 IL-23Ra variant with leucine at position 310 for potential therapeutic applications because it may serve as a decoy receptor for disease treatment. Id. at 6. In our view, however, the Examiner's interpretation of the prior art relies on improper hindsight gleaned from Appellants' Specification. Kan discloses the existence of alternatively spliced IL-23Ra mRNAs, but notes that some of these mRNAs may be degraded by "nonsense-mediated decay (NMD)." Kan 636. Kan indicates that the L'i8,9 variant might be among those degraded by NMD. See id. at 634, Fig. 2 (L'i8,9 variant annotated as"?" under "Target ofNMD Pathway"). Similarly, Kan refers to the L'i8,9 variant as among those "yielding potentially functional transcripts" and that generate "potential soluble receptors." Id. at 636, right and left cols., respectively. Finally, Kan indicates that "more studies are needed to clarify better the significance of the biological function of these IL-23Ra variants in activated human leukocytes." Id. at 637---638. Thus, Kan does not provide evidence that the L'i8,9 variant of IL-23Ra is actually produced in vivo or that, if produced, it acts as a decoy receptor for IL-23. In addition, Cosman's disclosure is ambiguous regarding whether a variation of HPR2/IL-23Ra having leucine at position 310, rather than proline as in Kan, is a naturally occurring variant. Cosman states that 6 Appeal2018-000349 Application 13/065,878 "variations of HPR2 polypeptides are provided as naturally occurring genomic variants of the HPR2 sequences disclosed herein; such variations may be incorporated into an HPR2 polypeptide." Cosman ,r 219. However, Cosman also states that "[a]s one example, a change from the Leu residue position 310 of SEQ ID NO: 21 to a Pro residue could be caused by a single change from 'T' to 'C' at position 1035 of SEQ ID NO: 19." Id. (emphasis added). Cosman does not disclose that an HPR2 variant having a proline at position 310 actually occurs naturally, nor does Cosman disclose what effect, if any, this substitution has on the activity of HPR2 or an alternatively spliced variation thereof that is missing exons 8 and 9. In summary, we conclude that the cited references do not provide sufficient reason to lead a person of ordinary skill in the art to modify Kan's IL-23Ra to replace the leucine residue at position 310 with a pro line residue, with a reasonable expectation that the resulting truncated version of IL-23Ra would be therapeutically useful as a decoy receptor for antagonizing IL-23 activity. We therefore reverse the rejection of claims 24--28 and 34--42 under 35 U.S.C. Â§ 103(a) based on Kan and Cosman. REVERSED 7